Supervisor View Full Details

• cancer/oncology
• neuroscience and mental health

• Medicine
• Surgery

• Gastroenterology
• Neurology
• Neurophysiology
• Oncology
• Pharmacology
• Physiology

Heading up a large, highly skilled and motivated research team at the interface of biomedical and translational research and focusing on personalised medicine approaches, Prof Prehn is the Director of the RCSI Centre for Systems Medicine (http://www.systemsmedicineireland.ie/). Prof Prehn holds two prestigious SFI Investigator programs focusing on molecular subtyping and biomarker and therapeutics development for the treatment of colorectal cancer, totalling ?3M. He has coordinated several EU projects such as the Systems Medicine Collaborative Project APO-DECIDE (www.apodecide.eu; ?3 Million, 7 European partners including 3 SMEs) which featured in the ?H2020 Successes' EU publication. He collaborates with Oncologists, Gastroenterologists, GI surgeons, Neurosurgeons and Pathologists in Ireland and internationally (Imperial College London, ICR, LMU, Dana Farber). The group is one of the few groups world-wide that have successfully begun to translate dynamic systems models of cell survival and apoptosis signalling into a clinical context, and has filed several patent applications.

Recent publications in Colorectal Cancer (CRC), Neurooncology and Neurology:
Lindner AU, Gut, 2016, PMID 27663504; Salvucci M, Clin Cancer Res, 2016, PMID 27649552; D'Orsi B, J Neurosci, 2016, PMID 27098698; O'Halloran PJ, Eur J Nucl Med Mol Imaging, PMID 26975402; Zakaria Z, Br J Cancer, 2016, PMID 26657652.

Regulation of cell survival and cell death pathways by oncogenic BRAF in colorectal cancer

This project aims to clinically validate and refine systems-based patient stratification tools for the treatment of colorectal cancer (CRC) for which the group has already successfully demonstrated clinical proof-of-concept. The project will focus on a subtype of colorectal cancer characterised by Microsatellite Instability (MSI), BRAF mutations, and high mutation rate (?Consensus Molecular Subtype 1?). These patients have generally a good prognosis when diagnosed early, but have a very poor prognosis once patients relapse, the cause of which is unknown. We will test the hypothesis that the genomic rearrangements in this subtype of colorectal cancer is associated with increased stress signalling, in particular the so called Endoplasmic Reticulum (ER) stress response, with increased antigen exposure, and with defective immune signalling upon relapse. The clinician scientists will avail of one of the best clinically annotated collections of CRC tissue established by the PI in collaboration with the RCSI Biobank, and will directly perform translational studies using ex vivo, patient-derived tumor models eastablished in the group in collaboration with the Departments of Surgery and Pathology. The clinician PhD will i) assess ER stress signalling and immunophenotypes in this subtype of CRC, ii) investigate whether these represent prognostic biomarkers that identify patients at risk of recurrence, iii) test new therapeutic approaches that influence ER stress signalling and imune checkpoints and re-sensitise these tumours to chemotherapy and, iv) develop new predictive biomarkers that stratify patient for these new therapeutics.